The objectives of this research are to determine the molecular effects of histones and histone modifications and to elicit their roles in cellular processes such as transcription, replication, chromosomal condensation, and differentiation. This program has evolved along two lines: (1) definition of histone modifications by determination of extent of modification during the cell cycle or in response to chemical agents; and (2) utilization of information gained in the first approach to maximize the content of a histone or a modified histone. The effects of histones and histone modifications upon chromatin structure are being investigated. These investigations employ cell synchrony methods, radiolabeling, circular dichroism, ultracentrifugation, DNA nuclease digestion, and various systems of electrophoresis.